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- A Atlasov, Kirill, et al.
(författare)
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1D photonic band formation and photon localization in finite-size photonic-crystal waveguides
- 2010
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Ingår i: OPTICS EXPRESS. - 1094-4087. ; 18:1, s. 117-122
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Tidskriftsartikel (refereegranskat)abstract
- A transition from discrete optical modes to 1D photonic bands is experimentally observed and numerically studied in planar photonic-crystal (PhC) L-N microcavities of length N. For increasing N the confined modes progressively acquire a well-defined momentum, eventually reconstructing the band dispersion of the corresponding waveguide. Furthermore, photon localization due to disorder is observed experimentally in the membrane PhCs using spatially resolved photoluminescence spectroscopy. Implications on single-photon sources and transfer lines based on quasi-1D PhC structures are discussed.
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- A Herrera, I, et al.
(författare)
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Comparing a multi-linear (STEP) and systemic (FRAM) method for accident analysis
- 2010
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Ingår i: RELIABILITY ENGINEERING and SYSTEM SAFETY. - London, UK : Elsevier Science B.V., Amsterdam.. - 0951-8320. ; 95:12, s. 1269-1275, s. 19-26
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Tidskriftsartikel (refereegranskat)abstract
- Accident models and analysis methods affect what accident investigators look for, which contributory factors are found, and which recommendations are issued. This paper contrasts the Sequentially Timed Events Plotting (STEP) method and the Functional Resonance Analysis Method (FRAM) for accident analysis and modelling. The main issue addressed in this paper is the comparison of the established multi-linear method STEP with the new systemic method FRAM and which new insights the latter provides for accident analysis in comparison to the former established multi-linear method. Since STEP and FRAM are based on a different understandings of the nature of accidents, the comparison of the methods focuses on what we can learn from both methods, how, when, and why to apply them. The main finding is that STEP helps to illustrate what happened, involving which actors at what time, whereas FRAM illustrates the dynamic interactions within socio-technical systems and lets the analyst understand the how and why by describing non-linear dependencies, performance conditions, variability, and their resonance across functions.
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- A Hulten, Maj, et al.
(författare)
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On the origin of the maternal age effect in trisomy 21 Down syndrome: the Oocyte Mosaicism Selection model
- 2010
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Ingår i: Reproduction. - 1470-1626 .- 1476-3990. ; 139:1, s. 1-9
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Forskningsöversikt (refereegranskat)abstract
- We have recently documented that trisomy 21 mosaicism is common in human foetal ovaries. On the basis of this observation we propose that the maternal age effect in Down syndrome (DS) is caused by the differential behaviour of trisomy 21 in relation to disomy 21 oocytes during development from foetal life until ovulation in adulthood. in particular, we suggest that trisomy 21 oocytes, lagging behind those that are disomic, may escape the timed pruning of the seven million in foetal life to the 300-400 finally selected for ovulation. The net effect of this preferential elimination will be an accumulation of trisomy 21 oocytes in the ovarian reserve of older women. We here highlight the implications of this Oocyte Mosaicism Selection (OMS) model with respect to the prevalent view that the maternal age effect is complex, dependent on many different biological and environmental factors. We examine conclusions drawn from recent large-scale studies in families, tracing DNA markers along the length of chromosome 21q between parents and DS children, in comparison to the OMS model. We conclude that these family linkage data are equally compatible with the maternal age effect originating from the accumulation of trisomy 21 oocytes with advancing maternal age. One relatively straightforward way to get to grips with what is actually going on in this regard would be to compare incidence of trisomy 21 oocytes (and their pairing configurations) in foetal ovaries with that in oocytes at the meiosis I stage from adult women.
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- A. Strumpfer, Johan, et al.
(författare)
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Stretching of Twitchin Kinase
- 2012
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Ingår i: Biophysical Journal. - St. Louis, MO, United States : Cell Press. - 0006-3495 .- 1542-0086. ; 102:3 Supplement 1, s. 361a-362a
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Tidskriftsartikel (refereegranskat)abstract
- The giant proteins from the titin family, that form cytoskeletal filaments, have emerged as key mechanotransducers in the sarcomere. These proteins contain a conserved kinase region, which is auto-inhibited by a C-terminal tail domain. The inhibitory tail domain occludes the active sites of the kinases, thus preventing ATP from binding. It was proposed that through application of a force, such as that arising during muscle contraction, the inhibitory tail becomes detached, lifting inhibition. The force-sensing ability of titin kinase was demonstrated in AFM experiments and simulations [Puchner, et al., 2008, PNAS:105, 13385], which showed indeed that mechanical forces can remove the autoinhibitory tail of titin kinase. We report here steered molecular dynamics simulations (SMD) of the very recently resolved crystal structure of twitchin kinase, containing the kinase region and flanking fibronectin and immuniglobulin domains, that show a variant mechanism. Despite the significant structural and sequence similarity to titin kinase, the autoinhibitory tail of twitchin kinase remains in place upon stretching, while the N-terminal lobe of the kinase unfolds. The SMD simulations also show that the detachment and stretching of the linker between fibronectin and kinase regions, and the partial extension of the autoinhibitory tail, are the primary force-response. We postulate that this stretched state, where all structural elements are still intact, may represent the physiologically active state.
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- Aagaard, Lise, et al.
(författare)
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Global Patterns of Adverse Drug Reactions Over a Decade Analyses of Spontaneous Reports to VigiBase (TM)
- 2012
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Ingår i: Drug Safety. - : Adis. - 0114-5916 .- 1179-1942. ; 35:12, s. 1171-1182
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Tidskriftsartikel (refereegranskat)abstract
- Background: Although systems to collect information about suspected adverse drug reactions (ADRs) were established in many countries and by the WHO in the 1960s, few studies have examined reported ADRs related to national income. Objective: The aim of the study was to characterize ADRs reported to the WHO-ADR database, VigiBase (TM), and to relate data to national income. Methods: We analysed ADR reports submitted to VigiBase (TM) from 2000 to 2009 with respect to reporting rate, age and sex of patient, type, seriousness and medications. Reports were also analysed with respect to national income level, classified in accordance with the World Bank definition: low, lower-middle, upper-middle and high. Results: We analysed 1 359 067 ADR reports including 3 013 074 ADRs. Overall, 16% of reports were serious and 60% were reported for females. High-income countries had the highest ADR reporting rates (range 3-613 reports/million inhabitants/year) and low-income countries the lowest (range 0-21). Distribution of ADRs across income groups with respect to age group, seriousness and sex was non-significant. Overall, the majority of ADRs were reported for nervous system medications, followed by cardiovascular medicines. Low-income countries reported relatively more ADRs for antiinfectives for systemic use than high-income countries, and high-income countries reported more ADRs for antineoplastic and immunomodulating agents than lower-income groups. Conclusion: This study showed that high-income countries had the highest ADR reporting rates and low-income countries the lowest, with large variations across countries in each group. Significant differences in ADR reporting rates were only found for ADRs of the type skin and subcutaneous tissue disorders and for the therapeutic groups antiinfectives for systemic use and antineoplastic and immunomodulation agents. To strengthen ADR reporting rates, especially in low-income countries, more research is needed about the impact of organizational structures and economic resources of national pharmacovigilance centres and ADR reporting practices on the large variations in ADR reporting rates within income groups.
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- Aamand Grabau, Dorthe, et al.
(författare)
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The prevalence of immunohistochemically determined oestrogen receptor positivity in primary breast cancer is dependent on the choice of antibody and method of heat-induced epitope retrieval - prognostic implications?
- 2013
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Ingår i: Acta Oncologica. - : Informa Healthcare. - 0284-186X .- 1651-226X. ; 52:8, s. 1657-1666
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Tidskriftsartikel (refereegranskat)abstract
- Background. Oestrogen receptor (ER) status is important for the choice of systemic treatment of breast cancer patients. However, most data from randomised trials on the effect of adjuvant endocrine therapy according to ER status are based on the cytosol methods. Comparisons with immunohistochemical methods have given similar results. The aim of the present study was to examine whether different ER antibodies and heat-induced epitope retrieval (HIER) methods influence the prevalence of ER-positivity in primary breast cancer. Material and methods. This study is based on patients included in a clinical trial designed to compare the effect of two years of adjuvant tamoxifen versus no adjuvant systemic treatment in premenopausal women. From 1986 to 1991, 564 patients from two study centres in Sweden were enrolled and randomised. Patients were randomised independently of ER status. In the present study, ER status was assessed on tissue microarrays with the three different ER antibody/HIER combinations: 1D5 in citrate pH 6 (n = 390), SP1 in Tris pH 9 (n = 390) and PharmDx in citrate pH 6 (n = 361). Results. At cut-offs of 1% and 10%, respectively, the prevalence of ER-positivity was higher with SP1 (75% and 72%) compared with 1D5 (68% and 66%) and PharmDx (66% and 62%). At these cut-offs, patients in the discordant groups (SP1-positive and 1D5-negative) seem to have a prognosis intermediate between those of the double-positive and double-negative groups. Comparison with the ER status determined by the cytosol-based methods in the discordant group also showed an intermediate pattern. The repeatability was good for all antibodies and cut-offs, with overall agreement andgt;= 93%. Conclusion. The present study shows that the choice of antibody and HIER method influences the prevalence of ER-positivity. We suggest that this be taken into consideration when choosing a cut-off for clinical decision making.
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| 10. |
- Aamir, Syed Ahmed, 1980-, et al.
(författare)
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A 1.2-V pseudo-differential OTA with common-mode feedforward in 65-nm CMOS
- 2010
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Ingår i: Proceedings of the 17th IEEE International Conference on Electronics, Circuits, and Systems. - : Institute of Electrical and Electronics Engineers (IEEE). ; , s. 29-32
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Konferensbidrag (refereegranskat)abstract
- In this work, we describe the implementation of a 1. 2-V pseudo-differential operational transconductance amplifier (OTA) with common-mode feedforward (CMFF) and inherent common-mode feedback (CMFB) in a 65-nm, digital CMOS process. The OTA architecture provides an inherent CMFB when cascaded OTA structures are utilized andthis work has studied a cascaded amplifier consisting of fourstages. Due to the low-gain using core 65-nm circuit devices, the overall gain must be distributed on all four stages to acquire a gain of more than 60 dB, while maintaining a-3-dB bandwidth of 200 MHz. To achieve high gain, we propose using a modified, positive-feedback, cross-coupled input differential stage. The modified OTA achieves a high output swing of ± 0.85 V due to only two stacked transistors, 88 dB DC gain and a third-order harmonic of -60 dB for 800 mVpp at 30 MHz. Further on, in a capacitive buffer configuration, we achieve a high slew rate of 1240 V/µS, -3-dB bandwidth of 509 MHz, signal-to-noise ratio of 63 dB while consuming 10.4 mW power.
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